Intensity-Modulated Radiation Therapy, Fluorouracil, and Mitomycin C in Treating Patients With Invasive Anal Cancer

Phase 2

Completed

Conditions: Anal Cancer

Interventions: Drug: fluorouracil
Drug: mitomycin C
Radiation: Intensity-modulated radiation therapy

Registration Number: NCT00423293

Lead Sponsor: Radiation Therapy Oncology Group

Brief Summary: RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as fluorouracil and mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with 5-fluorouracil (5-FU) and mitomycin C may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving intensity-modulated radiation therapy together with fluorouracil and mitomycin C works in treating patients with invasive anal cancer.

Detailed Description: OBJECTIVES:

Primary

* Determine if dose-painted, intensity-modulated radiation therapy (IMRT), fluorouracil, and mitomycin C decreases the combined rate of gastrointestinal and genitourinary adverse events (grade II or greater) by at least 15% in the first 90 days after the start of treatment in patients with primary invasive carcinoma of the anal canal compared to patients treated on the radiotherapy, fluorouracil, and mitomycin C arm on clinical trial RTOG 98-11.

Secondary

* Determine the feasibility of performing IMRT in these patients in a cooperative group setting.

* Evaluate adverse events experienced by patients treated with this regimen and to decrease the grade 2 and higher and grade 3 and higher overall adverse event rates by 15% or 20% as compared to the radiotherapy and mitomycin C arm of RTOG 98-11.

* Evaluate the total duration of radiotherapy.

* Evaluate the efficacy of this regimen, in terms of locoregional failure, disease-free survival, time to colostomy, colostomy-free survival, and overall survival of these patients.

* Determine clinical complete response at 8 weeks after completion of study treatment.

OUTLINE: This is a multicenter study.

Patients receive mitomycin C IV over 10-30 minutes on days 1 and 29 and fluorouracil IV continuously over 96 hours on days 1-4 and 29-32. Patients also undergo dose-painted intensity-modulated radiation therapy once daily, 5 days a week, for 5½ to 6 weeks beginning on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 59 patients will be accrued for this study.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 63

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
5-FU + Mitomycin + IMRT	fluorouracil	5-FU + Mitomycin + IMRT
5-FU + Mitomycin + IMRT	Intensity-modulated radiation therapy	5-FU + Mitomycin + IMRT
5-FU + Mitomycin + IMRT	mitomycin C	5-FU + Mitomycin + IMRT

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects With Acute Gastrointestinal (GI) and Genitourinary (GU) Adverse Events (AE) ≥ Grade 2 as Defined by CTCAE v3.0 (Common Terminology Criteria for Adverse Events)	From the start of treatment to 90 days	Highest grade adverse event per subject were counted. Adverse events were graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Acute toxicities occur within 90 days of the start of treatment.

Secondary Outcome Measures

Name	Time	Method
Five-year Rate of Overall Survival	From registration to 5 years	Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.
Number of Patients With Major Radiation Planning Deviations	Planning occurred prior to radiation therapy	Deviations in intensity-modulated radiation therapy technique (IMRT) planning were determined by central review by the radiation oncology co-chairs of the study.
Percentage of Subjects With Acute Adverse Events (AE)	From the start of treatment to 90 days	Highest grade adverse event per subject were counted. Adverse events were graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Acute toxicities occur within 90 days of the start of treatment.
Percentage of Subjects With Late Adverse Events (AE)	From 91 days after start of study treatment to the end of follow-up. Maximum follow-up at time of analysis was 9.2 years.	Highest grade adverse event per subject were counted. Adverse events were graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Late toxicities occur greater than 90 days from the start of treatment.
Clinical Complete Response Rate	8 and 12 weeks after treatment completion (corresponding to 14 and 18 weeks from registration)	A complete clinical response was defined as complete resolution of all palpable tumor determined by digital rectal exam and proctosigmoidoscopy supplemented with pelvic axial imaging.
Five-year Rate of Disease-free Survival	From registration to 5 years	Disease-free survival time is defined as time from registration to the date of local-regional failure, the appearance of distant metastases, the appearance of a second primary failure, or date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive without failure are censored at the date of last contact. Local failure is defined as any measurable disease after 12 weeks from the completion of chemoradiation therapy. Local failure is defined as: a) For patients with no disease in pelvic and/or groin nodes, the appearance of disease in pelvic or groin nodes; b) For patients with disease in pelvic and/or groin nodes at study entry, nodal recurrence following clearance or persistent nodal disease for more than 12 weeks after completion of treatment.
Five-Year Rate of Colostomy-free Survival	From registration to 5 years	Colostomy-free survival time is defined as time from registration to date of colostomy or abdominoperineal (A-P) resection, or date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive without failure are censored at the date of last contact.
Duration of Radiotherapy Treatment	From start to end of radiation therapy (6 weeks)	Number of days from radiotherapy treatment start to radiotherapy treatment end
Five-Year Cumulative Incidence Rate of Local-regional Failure	From registration to 5 years	Local-regional failure time is defined as time from registration to date of failure and is estimated by the cumulative incidence method. Patients last known to be alive without failure are censored at the date of last contact. Local-regional failure is defined as a local or regional failure. Local failure is defined as any measurable disease after 12 weeks from the completion of chemoradiation therapy. Regional failure is defined as: a) For patients with no disease in pelvic and/or groin nodes, the appearance of disease in pelvic or groin nodes; b) For patients with disease in pelvic and/or groin nodes at study entry, nodal recurrence following clearance or persistent nodal disease for more than 12 weeks after completion of treatment.
Five-Year Cumulative Incidence Rate of Distant Failure	From registration to 5 years	Distant failure time is defined as time from registration to the appearance of distant metastases and is estimated by the cumulative incidence method. Patients last known to be alive without failure are censored at the date of last contact.
Five-Year Cumulative Incidence Rate of Colostomy Failure	From registration to 5 years	Colostomy failure time is defined as time from registration to the date of colostomy or abdominoperineal (A-P) resection and is estimated by the cumulative incidence method. Patients last known to be alive without failure are censored at the date of last contact.

Trial Locations

Locations (172): Arizona Oncology - Tucson
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Tucson, Arizona, United States
Auburn Radiation Oncology
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Auburn, California, United States
Providence Saint Joseph Medical Center - Burbank
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Burbank, California, United States
Radiation Oncology Centers - Cameron Park
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Cameron Park, California, United States
Mercy Cancer Center at Mercy San Juan Medical Center
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Carmichael, California, United States
City of Hope Comprehensive Cancer Center
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Duarte, California, United States
USC/Norris Comprehensive Cancer Center and Hospital
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Los Angeles, California, United States
Radiation Oncology Center - Roseville
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Roseville, California, United States
Radiological Associates of Sacramento Medical Group, Incorporated
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Sacramento, California, United States
Mercy General Hospital
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Sacramento, California, United States
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Arizona Oncology - Tucson
🇺🇸Tucson, Arizona, United States